J Mol Med DOI 10.1007/s00109-014-1193-7

ORIGINAL ARTICLE

Mutual amplification of corticosteroids and angiotensin systems in human vascular smooth muscle cells and carotid atheroma Hanène Ayari & Liliana Legedz & Catherine Cerutti & Pierre Lantelme & Patrick Feugier & Marie-Paule Gustin & Olivier Lohez & Ali Nehme & Jacques Yuan Li & Jouda Gharbi-Chihi & Giampiero Bricca

Received: 30 October 2013 / Revised: 16 June 2014 / Accepted: 10 July 2014 # Springer-Verlag Berlin Heidelberg 2014

Abstract The involvement of the renin-angiotensin-aldosterone system (RAAS) and cortisol in increased cardiovascular risk is well known. If numerous relationships between RAAS and corticosteroids have been described, their interactions within the arterial wall, especially during the transdifferentiation of vascular smooth muscle cells (VSMCs) and the atheroma formation, are not established. Here, we clarified the relationships between mRNA levels of corticosteroid and angiotensin system components using cortisol, fludrocortisone, and angiotensin II treatments of cultured VSMCs maintained in a contractile phenotype or induced to a lipid storing phenotype. We then determined the quantitative relationships between the mRNA content of these components measured with reverse transcription polymerase chain reaction (RT-PCR), in the atheroma plaque and nearby macroscopically intact tissue (MIT) from 27 human carotid endarterectomy samples. In both VSMC phenotypes, cortisol markedly increased both angiotensinogen (AGT) and AT1-receptor (AT1R) mRNA levels. These effects of cortisol were mediated via glucocorticoid receptor-α (GRα) without any illicit activation of the mineralocorticoid receptor (MR). Angiotensin II increased GRα, 11βHSD1, CYP11B1, as well as CYP11B2 mRNAs Hanène Ayari and Liliana Legedz contributed equally to the work. Electronic supplementary material The online version of this article (doi:10.1007/s00109-014-1193-7) contains supplementary material, which is available to authorized users. H. Ayari : L. Legedz : C. Cerutti : P. Lantelme : P. Feugier : M.

Mutual amplification of corticosteroids and angiotensin systems in human vascular smooth muscle cells and carotid atheroma.

The involvement of the renin-angiotensin-aldosterone system (RAAS) and cortisol in increased cardiovascular risk is well known. If numerous relationsh...
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